Hyper-Expression of PD-1 Is Associated with the Levels of Exhausted and Dysfunctional Phenotypes of Circulating CD161++TCR iVα7.2+ Mucosal-Associated Invariant T Cells in Chronic Hepatitis B Virus Infection

Frontiers in Immunology

卷:9

Ramachandran Vignesh¹  Adeeba Kamarulzaman²  Jayakumar Rajarajeswaran³  James E. Ussher⁴  Vijayakumar Velu⁵  Esaki M. Shankar⁷  Yean K. Yong⁸  Rami Al Batran⁹  Jamuna Vadivelu⁹  Abdul W. Ansari¹⁰  Mohamed Rosmawati¹⁰  Alireza Saeidi¹⁰  V. Vasuki¹¹  Hong Y. Tan¹²  Indranil Chattopadhyay¹³  Marie Larsson¹⁴  Philip F. Enström¹⁴  Amudhan Murugesan¹⁶ 

[1] 0Laboratory-Based Department, Universiti Kuala Lumpur, Ipoh, Malaysia;

[2] 1Center of Excellence for Research in AIDS, University of Malaya, Kuala Lumpur, Malaysia;

[3] 2Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia;

[4] 3Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand;

[5] 4Department of Microbiology and Immunology, Emory Vaccine Center, Atlanta, GA, United States;

[6] 5Division of Infection Biology, Department of Life Sciences, Central University of Tamil Nadu, Thiruvarur, India;

[7] 6Department of Microbiology, Central University of Tamil Nadu, Thiruvarur, India;

[8] China-ASEAN Institute of Marine Science (CAMS), Xiamen University Malaysia, Sepang, Malaysia;

[9] Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia;

[10] Department of Medicine, University of Malaya Medical Centre, Kuala Lumpur, Malaysia;

[11] Department of Microbiology, The Government Thiruvarur Medical College and Hospital, Thiruvarur, India;

[12] Department of Traditional Chinese Medicine, Xiamen University Malaysia, Sepang, Malaysia;

[13] Division of Molecular Cancer Biology, Department of Life Sciences, Central University of Tamil Nadu, Thiruvarur, India;

[14] Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden;

[15] Laboratory Center, Xiamen University Malaysia, Sepang, Malaysia;

[16] The Government Theni Medical College and Hospital, Theni, India;

关键词: HBV infection;    HLA-DR;    immune exhaustion;    immunosenescence;    mucosal-associated invariant T cells;    PD-1;   

DOI  :  10.3389/fimmu.2018.00472

来源: DOAJ

【 摘 要 】

Mucosal-associated invariant T (MAIT) cells, defined as CD161++TCR iVα7.2+ T cells, play an important role in the innate defense against bacterial infections, and their functionality is impaired in chronic viral infections. Here, we investigated the frequency and functional role of MAIT cells in chronic hepatitis B virus (HBV) infection. The peripheral CD3+CD161++TCR iVα7.2+ MAIT cells in chronic HBV-infected patients and healthy controls were phenotypically characterized based on CD57, PD-1, TIM-3, and CTLA-4, as well as HLA-DR and CD38 expression. The frequency of MAIT cells was significantly decreased among chronic HBV-infected individuals as compared to controls. Expression of CD57, PD-1, CTLA-4, as well as HLA-DR and CD38 on MAIT cells was significantly elevated in chronic HBV-infected individuals relative to controls. The percentage of T cell receptor (TCR) iVα7.2+ CD161+ MAIT cells did not correlate with HBV viral load but inversely with HLA-DR on CD4+ T cells and MAIT cells and with CD57 on CD8+ T cells suggesting that decrease of MAIT cells may not be attributed to direct infection by HBV but driven by HBV-induced chronic immune activation. The percentage and expression levels of PD-1 as well as CTLA-4 on MAIT cells inversely correlated with plasma HBV-DNA levels, which may suggest either a role for MAIT cells in the control of HBV infection or the effect of HBV replication in the liver on MAIT cell phenotype. We report that decrease of TCR iVα7.2+ MAIT cells in the peripheral blood and their functions were seemingly impaired in chronic HBV-infected patients likely because of the increased expression of PD-1.

【 授权许可】

Unknown